Vaccines offer the most effective prophylactic measure known against viral diseases however, most are not administered until weeks or months after birth due to inactivation by maternally derived antibodies and legitimate safety concerns for the neonate. Work from this laboratory and others have recently shown that vaccination within hours of birth with plasmid DNA can prime long-lived antiviral immunity. Plasmid vaccines are particularly effective at inducing cell mediated immune responses critical for protection against most viruses. Preliminary data presented here also demonstrates that DNA vaccination even prior to birth can also result in the development of protective antiviral immunity which persists into adulthood. Vitally infected neonates and premature infants suffer more damaging disease sequelae than infected children and adults therefore DNA vaccination early in life even prior to birth could be an attractive alternative to conventional vaccines among this highly at-risk population. Despite a number of reports documenting the efficacy among neonates of antiviral DNA vaccines we still know very little about how the very young respond to DNA vaccination This proposal will examine qualitative and quantitative aspects of cell mediated antiviral immune responses induced by DNA vaccination in prenatal and early postnatal life. This approach will allow us to determine if the fundamental mechanisms driving cell mediated immune responses in adulthood operate as effectively early in life after prenatal or early post-natal DNA immunization. Thus the aims are to 1) Refine our prenatal DNA delivery system to permit prenatal vaccination after maternal DNA administration 2) Determine how soon after prenatal and neonatal DNA vaccination antiviral effector responses necessary for protective immunity develop. 3) Examine the antigen specific T cell repertoire arising after prenatal and neonatal DNA vaccination to determine if early vaccination leads to the acquisition of antigen specific T cells which are structurally similar to those which develop in vaccinated adults.